1999 Jonathan E. Rhoads lecture. Isotopic metaprobes, nutrition, and the roads ahead

The 1999 Jonathan E. Rhoads lecture, delivered by Vernon R. Young at the annual meeting of American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), San Diego, February 2, 1999, with the printed version coauthored with Alfred M. Ajami, is concerned with the application of isotopic probes and how, in particular, they may be used as diagnostic tools to enhance the role of nutrition in the comprehensive medical management of the patient. Following a brief review of the early uses of stable isotopes in metabolic research we consider the present and possible future application of stable isotope probes. The concept of a "gateway" enzyme in a discrete biochemical pathway and how the flow of substrate through this step might be assessed by giving a "metaprobe" is developed. The specific and desirable structural requirements of the metaprobe are considered. A number of examples are given that further exploit the concepts of "underground" metabolism and of metabolic "hijackers." It is our view that we are on the verge of a new era where, for the many pragmatic and exciting reasons discussed, stable isotope probes will find and increasing use in the practice of clinical medicine and in the preventive and public health areas.